Aerosol Cyclosporine Improves Lung Function After Transplant

VIENNA (Reuters Health) – For some lung transplant patients, an aerosol form of cyclosporine can effectively maintain and improve lung function, U.S. researchers told the International Society for Heart and Lung Transplant annual meeting on Thursday.

Researchers from the University of Pittsburgh Medical Centre and elsewhere said the response was dose-dependent, with the benefits limited to patients who received more than 5 mg of the drug in the periphery of their transplanted lung.

The results come from a subanalysis of 15 patients from an ongoing 68-patient study. The reseachers hypothesise that an aerosolised form of the drug will achieve higher lung concentrations than intravenous or oral administration. Inhaling the drug directly might also avoid systemic infections or complications.

“There is reason to believe that this drug, when given in addition to systemic immunosuppression, may improve overall outcomes for lung transplant recipients who received the drug compared to patients given placebo, and final results are being analysed,” said lead investigator Dr. Aldo T. Iacono in a statement.

“This most recent analysis–our first from the 68-patient study–indicates that aerosol cyclosporine specifically enhances lung function in patients who deposit higher concentrations of the drug.” In the trial, single- and double-lung transplant patients were randomised to receive 300-mg aerosol cyclosporine as an adjuvant therapy along with standard oral immunosuppression, most often tacrolimus, or placebo.

The current analysis involved 15 patients who underwent radio-imaging about 6 months after transplant to measure deposition of the drug, to assess the dose-response relationship.

“Because anatomy and physiology differ from patient to patient, the drug is deposited in tissue in varying degrees,” said co-investigator Dr. Timothy E. Corcoran, who reported the findings at the meeting.

Single-lung transplant recipients absorbed between 2.2% and 9.2% of the dose in their transplanted lung and double-lung transplant recipients deposited between 3.3% and 7.1%.

The researchers then measured changes in lung function by comparing a patient’s best FEV1 before post-op day 100 and measurements taken every 100 days up to 700 days.

Patients who deposited at least 5 mg of the drug showed significant improvement in lung function over time, whereas patients who deposited less than 5 mg and patients given placebo demonstrated decline in lung function over the same period.

“Aerosol cyclosporine appears to have a cumulative positive effect because there was a significant correlation between improvement in lung function tests and dose at all time points studied,” Dr. Corcoran commented. “Furthermore, the percentage change in lung function increased with each milligram of drug deposited in the periphery of the lung.”